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利用波导微流控芯片捕获和临床应用循环肿瘤细胞。

Capturing and Clinical Applications of Circulating Tumor Cells with Wave Microfluidic Chip.

机构信息

School of Mathematics and Physics of Science and Engineering, Anhui University of Technology, Maanshan, 243002, China.

Division of Nanobionic Research, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, Jiangsu, China.

出版信息

Appl Biochem Biotechnol. 2020 Apr;190(4):1470-1483. doi: 10.1007/s12010-019-03199-4. Epub 2019 Nov 28.

Abstract

As a "liquid biopsy," circulating tumor cell (CTC) enumeration with microfluidic chips has great significance in cancer prognosis. CTCs carry significant information as the original tumor. Integrated microfluidic chips are combining with affinity- and physical-based such as wave chip offers a new way to segregate CTCs. In this work, we further study capturing clinical applications of CTCs with wave chip. When cell suspension moves across the microposts array, CTCs squeeze out from narrow gaps organized by microposts. This movement renders CTCs to obtain a tilted velocity to fluid direction. This tilted velocity would direct CTCs to be captured by the smaller neighboring gaps next array. Simultaneously, interaction or friction time is longer due to barrier of modified microposts. These microposts would be effective for realizing binding of antigen and antibody. Therefore, both antibody-coated and physical-based isolations could be combined in isolating CTCs. Capture percentage concentrated on the first several arrays is shown theoretically and experimentally. Efficient capture could be obtained for artificial patient blood. Clinically, CTCs were tested positive for three metastatic human breast cancer patient samples. This wave chip is prospectively to be a valid tool for clinical enumeration of CTCs, carrying out anti-cancer drug assay.

摘要

作为一种“液体活检”,利用微流控芯片对循环肿瘤细胞(CTC)进行计数对癌症预后具有重要意义。CTC 携带的原始肿瘤信息具有重要意义。集成微流控芯片正在结合基于亲和力和物理性质的方法,如波片,为分离 CTC 提供了一种新方法。在这项工作中,我们进一步研究了使用波片进行 CTC 临床应用的捕获。当细胞悬浮液穿过微柱阵列时,CTC 从微柱组织的狭窄间隙中挤出。这种运动使 CTC 获得相对于流体方向的倾斜速度。这种倾斜速度会使 CTC 被下一个阵列中较小的相邻间隙捕获。同时,由于改性微柱的阻挡,相互作用或摩擦时间会更长。这些微柱将有效地实现抗原和抗体的结合。因此,抗体包被和基于物理的分离都可以结合起来分离 CTC。理论和实验都显示了前几个阵列上的浓缩捕获百分比。对于人工患者血液,可以获得高效的捕获。临床上,从 3 名转移性人类乳腺癌患者样本中检测到 CTC 呈阳性。这种波片有望成为临床 CTC 计数的有效工具,进行抗癌药物检测。

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